title: In vitro toxic action potential of anti tuberculosis drugs and their combinations.
abstract: Tuberculosis (TB) is one of the leading infectious causes of death due to single infectious agent after HIV/AIDS. Rifampicin (RIF), Isoniazid (INH), Ethambutol (EMB), Pyrazinamide (PZA) and/or their combinations are extensively prescribed to treat TB. Despite several therapeutic implications, these drugs also produce several toxic effects at cellular level. MTT assay and Ames test were adopted in this study for the determination of cytotoxic and mutagenic potential of these anti-TB drugs. Among all tested drugs, cytotoxic potential of RIF was strongest with highly significant decline (p<0.001) in cell numbers at the concentration of 250μg/ml with LC50 at 325μg/ml, while significant decline (p<0.01) in cell count was observed in INH treated group at the concentration 500μg/ml with LC50 at 1000μg/ml. Moreover, combination RIPE demonstrated significant reduction (p<0.01) in cell number at the concentration of 25-500-500-500μg/ml with LC50 at 60-1200-1200-1200μg/ml. It is apparent from the data that almost all drugs represented identical mutagenic pattern i.e., more significant results were achieved in TA100 with metabolic activation (+S9). RIF proved to be highly mutagenic of all tested drugs with significant mutagenicity (p<0.01) at 0.0525μg/plate against TA98 strain with S9. The combination RIPE exhibited highly significant mutagenic activity (p<0.01) at concentration 0.125-3-3-3μg/plate without S9, while addition of S9 resulted in similar activity at lower doses, i.e., 0.0525-1-1-1μg/plate. It was concluded from the data that all anti-TB drugs possess significant cytotoxic and mutagenic potential, especially in combination, making TB patient more vulnerable to cytotoxic and mutagenic effects of anti-TB drugs, which could produce further health complications in TB patients.
authors.affiliation: Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
authors.forename: Riffat
authors.initials: R
authors.lastname: Fatima
authors.affiliation: Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan. Electronic address: drashraf2001@yahoo.com.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ashraf
authors.affiliation: Department of Clinical Neurosciences, Neurology Unit, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK. Electronic address: Se298@cam.ac.uk.
authors.forename: Sohail
authors.initials: S
authors.lastname: Ejaz
authors.affiliation: Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
authors.forename: Muhammad Adil
authors.initials: MA
authors.lastname: Rasheed
authors.affiliation: Microbiology Section, Quality Operations Laboratory, University of Veterinary and Animal Sciences, Lahore, Pakistan.
authors.forename: Imran
authors.initials: I
authors.lastname: Altaf
authors.affiliation: Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
authors.forename: Misbah
authors.initials: M
authors.lastname: Afzal
authors.affiliation: Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
authors.forename: Zainab
authors.initials: Z
authors.lastname: Batool
authors.affiliation: Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
authors.forename: Umber
authors.initials: U
authors.lastname: Saleem
authors.affiliation: Department of Pharmacology and Toxicology, University of Veterinary and Animal Sciences, Lahore, Pakistan.
authors.forename: Khaleeq
authors.initials: K
authors.lastname: Anwar
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004359:Drug Therapy, Combination; D020128:Inhibitory Concentration 50; D009152:Mutagenicity Tests; D009154:Mutation; D018570:Risk Assessment; D012475:Salmonella / Q000187:drug effects* / Q000235:genetics; D018675:Toxicity Tests / Q000379:methods
chemical_list: D000995:Antitubercular Agents
keywords: Ames test; Ethambutol; Isoniazid; MTT assay; Pyrazinamide; Rifampicin